Lypolytic modulation in adipocytes by adenylate cyclase effectors is due to changes in cellular cAMP concentration, measured indirectly by assessing the activation state of cAMP-dependent protein kinase (A-kinase). Insulin, by contrast, exhibits both cAMP-related and -independent antilipolytic actions. Moreover, loss of the cAMP-independent insulin effect is related to increased kinase activity, suggesting that this mode of insulin action represents activation of a phosphatase that inactivates the lipase. The above insulin actions are seen both in cells stimulated by addition of lipolytic hormones and in cells stimulated by removal of adenylate cyclase inhibitor, adenosine in this case. However, hormone-stimulated cells are 5-times more sensitive to insulin than are cells stimulated by adenosine removal, and this phenomenon occurs with both cAMP-related and -independent insulin actions. The key observation is that occupancy of adenylate cyclase-associated receptors modifies insulin action on processes apparently unrelated to cellular cAMP concentrations, a conclusion supported by glucose-transport studies. Although beta adrenergic agonists decrease and adenosine receptor agonists increase insulin-stimulated transport, neither affect appears to be attributable to changes in A-kinase activity. The above studies answer long-standing questions on the importance of insulin's ability to lower cAMP in inhibiting lipolysis. Under conditions of moderate lipolytic activity insulin acts primarily by decreasing cAMP, but at relatively high lipolytic rates insuling acts via a cAMP-independent mechanism, presumably a phosphatase activation. Perhaps more importantly, the data indicate that adenylate cyclase-linked receptors regulate insulin actions quite independent of any effects they might have cellular cAMP concentrations, suggesting that these receptors are associated also with molecules other than adenylate cyclase.